Further Analyses from CARGO II at ISHLT Characterize Utility of cfDNA and Impact on Monitoring Heart Transplant Recipients on Rejection Medication

April 16, 2015 — CareDx Inc., a molecular diagnostics company focused on the development and commercialization of clinically differentiated, high-value, non-invasive surveillance solutions for transplant recipients, announced new evidence that the proportion of cell-free DNA (cfDNA) derived from the transplanted organ and found in the bloodstream of the recipient is correlated to the rejection status of the organ. This new biomarker (cfDNA) in combination with AlloMap, the company's molecular diagnostic surveillance solution, provides greater accuracy of identification of rejection in heart transplant recipients than either test alone.

The analyses of blood samples from a subset of patients from the multicenter Cardiac Allograft Rejection Gene expression Observational study II (CARGO II) heart transplant observational study represent the first time that researchers have measured both cfDNA and gene expression profiles (AlloMap) in blood samples taken from the same patients. Dr. Maria G. Crespo-Leiro, a cardiologist from Hospital Universitario A Coru?a in Spain, presented the results today at the 35th Annual Meeting and Scientific Sessions of the International Society for Heart and Lung Transplantation (ISHLT) held in Nice, France.

“While we’ve known that AlloMap can be used to rule out rejection in selected patients, now we have evidence that cfDNA is a promising biomarker to further assess the likelihood of heart-transplant rejection. These two non-invasive blood tests are complementary to one another and promise to further increase our knowledge of the status of a transplant recipient,” said Dr. Crespo-Leiro.

Researchers found that the proportion of donor-derived cfDNA in blood was significantly higher (about 1.7 fold higher, P=0.017) in patients who had a biopsy-confirmed rejection compared to blood transplant recipients who did not have rejection at the time of blood sampling. The mean AlloMap score was on average 4 points higher in patients with biopsy-confirmed rejection than AlloMap scores in patients with no rejection (P=0.007).

The clinical performance of a combination of the two tests resulted in a 10 percent increase in overall accuracy compared to the performance of either of the tests alone.

“The clinical use of AlloMap has continued to grow since its recommendation for non-invasive monitoring of acute heart transplant rejection in the 2010 ISHLT evidence-based guidelines for patient care,” said

James Yee, M.D., Ph.D., chief medical officer at CareDx. “The new results presented today are exciting because they show the promise that the management of patients may be further enhanced when information from cfDNA is added to the AlloMap score. CfDNA levels rise as a signal of damage to the cardiac cells whereas the AlloMap score reflects the relative activation of the recipient’s immune system: these two signals provide complementary information that is helpful to more accurately estimate the risk of rejection at the time of testing. CareDx is sponsoring an ongoing study, named D-OAR, to further confirm the clinical performance of the cfDNA along with AlloMap.”